Patients with panic disorder have decreased platelet alpha 2 adrenoreceptors and increased adrenergic reactivity. Familial factors contribute substantially to the etiology of panic disorder, and mounting evidence suggests a specific genetic factor. Our aim is to determine if the observed adrenergic alterations in patients with panic disorder are state markers of the active panic disorder, or are more enduring characteristics that may reflect genetic factors. Specifically, we will test the following hypotheses: 1) panic patients have altered adrenergic function, 2) these alterations return to normal during remission, 3) symptom-free relatives of panic patients will not show adrenergic alterations, and 4) these adrenergic factors will significantly correlate with severity of anxiety symptoms. Four groups will be studied: drug-free patients with DSM-III-R panic disorder diagnosed by structured clinical interview (N=40), first degree relatives of these patients (N=40), normal controls (N=40), and first degree relatives of these controls (N=20). Dependent variables w ill include: a) platelet alpha 2 adrenoreceptor binding of clonidine and yohimbine, b) lying and standing: pulse, blood pressure, plasma epinephrine and plasma norepinephrine, c) standardized ratings of psychiatric symptoms. Data will be gathered for patients and matched controls at four times: 1) at initial evaluation, 2) two months after initial evaluation, 3) whenever a patient's panic attacks are in remission and treatment is about to be discontinued, and 4) one month after treatment ends during continued remission. Both groups of relatives will be studied only at baseline. Abnormalities that are found to be state markers of active panic disorder should offer insight into the mechanisms that mediate panic symptoms. Abnormalities found in both panic patients in remission and their asymptomatic relatives are likely to be genetically transmitted traits that will offer clues to the etiology of panic disorder. Abnormalities found in remitted patients but not in relatives are likely to be non-genetically transmitted markers that indicate a history of panic disorder. This study will advance our understanding of the possible etiologic significance of the physiological abnormalities associated with panic disorder.